Phenotypes associated with this allele

• Allele Symbol: Il33^{tm1(KOMP)Vlcg}
• Allele Name: targeted mutation 1, Velocigene
• Allele ID: MGI:4452857
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Il33^tm1(KOMP)Vlcg/Il33^tm1(KOMP)Vlcg	C57BL/6-Il33^tm1(KOMP)Vlcg	MGI:5790841

Genotype
MGI:5790841

hm1

• Allelic Composition: Il33^{tm1(KOMP)Vlcg}/Il33^{tm1(KOMP)Vlcg}
• Genetic Background: C57BL/6-Il33^{tm1(KOMP)Vlcg}
• Cell Lines: 12663E-H2

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

reproductive system

abnormal ovary morphology ( J:232676 )

♀ • accumulation of autofluorescent material in ovaries, starting as early as 3-5 weeks (puberty), rapidly increasing after 5-7 weeks (sexually mature), and becoming massive at 15-20 weeks (reproductive peak), greatly expanding the interstitial tissue

♀ • 3.2-fold faster accumulation of autofluorescent material relative to wild-type ovaries

♀ • numerous spherical bodies emitting autofluorescence with diameters of 20-60 um

decreased corpora lutea number ( J:232676 )

♀ • significantly fewer corpora lutea at 15-20 weeks (reproductive peak) relative to wild-type controls

abnormal ovarian follicle morphology ( J:232676 )

♀ • numerous autofluorescence-emitting spherical bodies, each surrounded by cells resembling theca cells and containing degrading organelles, myelin figures and granulosa cell nuclei, indicating abnormally collapsing atretic follicles abundant with lipofuscin

impaired ovarian folliculogenesis ( J:232676 )

♀ • significantly fewer total developing follicles at 15-20 weeks (reproductive peak), with marked decrease in type 3, 4, and 7 developing follicles relative to wild-type controls

abnormal ovary physiology ( J:232676 )

♀ • impaired disposal of atretic follicles, resulting in massive accumulation of tissue wastes abundant with aging-related catabolic wastes such as lipofuscin

♀ • accelerated ovarian aging and functional decline

early reproductive senescence ( J:232676 )

♀ • average reproductive life span (age for last successful delivery of a litter) is shortened to two thirds of that in heterozygous littermates

♀ • females deliver fewer litters than heterozygous littermates (3.15 +/- 0.61 versus 5.90 +/- 0.48) during their entire reproductive life span

decreased superovulation rate ( J:232676 )

♀ • upon equine chorionic gonadotropin/hCG-induced superovulation at 15-20 weeks, the number of ovulated eggs is reduced to 65% of age-matched wild-type controls

behavior/neurological

impaired passive avoidance behavior ( J:251814 )

• fear-based passive avoidance tests show a higher re-entry rate into the dark chamber post electric shock training in 60-80 week old mice, suggesting a loss of short memory

abnormal habituation to a new environment ( J:251814 )

• in habituation tests, 60-80 week old mice do not show a decline in exploration activities post training as wild-type controls

increased vertical activity ( J:251814 )

• mice show an age-related increase in vertical activity after 60 weeks of age

increased locomotor activity ( J:251814 )

• mice show an age-related increase in horizontal activity after 60 weeks of age

• however, older mice show no differences in motor function assessment on the RotaMex

homeostasis/metabolism

abnormal autophagy ( J:232676 , J:251814 )

• mice show a decrease in autophagy as indicated by a reduction of LC3 at 40 weeks prior to the onset of neuron loss and an increase in ubiquitinated proteins (J:251814)

• mice exhibit an accumulation of numerous vesicles or vacuoles in neural soma and neurites at 60 weeks of age with many of them double-membraned indicating abnormal accumulation of autophagosomes (J:251814)

♀ • diminished autophagy in atretic follicles, as shown by greatly reduced ovarian LC3-II protein, absence of LC3+ subcellular autophagosomes, and appearance of autofluorescent lipofuscin (J:232676)

abnormal double-strand DNA break repair ( J:251814 )

• mice fail to initiate the repair of rapidly increasing DNA double-strand breaks in stressed cortical and hippocampal neurons after an abrupt aging surge at 40 weeks of age

endocrine/exocrine glands

abnormal ovary morphology ( J:232676 )

♀ • accumulation of autofluorescent material in ovaries, starting as early as 3-5 weeks (puberty), rapidly increasing after 5-7 weeks (sexually mature), and becoming massive at 15-20 weeks (reproductive peak), greatly expanding the interstitial tissue

♀ • 3.2-fold faster accumulation of autofluorescent material relative to wild-type ovaries

♀ • numerous spherical bodies emitting autofluorescence with diameters of 20-60 um

decreased corpora lutea number ( J:232676 )

♀ • significantly fewer corpora lutea at 15-20 weeks (reproductive peak) relative to wild-type controls

abnormal ovarian follicle morphology ( J:232676 )

♀ • numerous autofluorescence-emitting spherical bodies, each surrounded by cells resembling theca cells and containing degrading organelles, myelin figures and granulosa cell nuclei, indicating abnormally collapsing atretic follicles abundant with lipofuscin

impaired ovarian folliculogenesis ( J:232676 )

♀ • significantly fewer total developing follicles at 15-20 weeks (reproductive peak), with marked decrease in type 3, 4, and 7 developing follicles relative to wild-type controls

abnormal ovary physiology ( J:232676 )

♀ • impaired disposal of atretic follicles, resulting in massive accumulation of tissue wastes abundant with aging-related catabolic wastes such as lipofuscin

♀ • accelerated ovarian aging and functional decline

cellular

abnormal autophagy ( J:232676 , J:251814 )

• mice show a decrease in autophagy as indicated by a reduction of LC3 at 40 weeks prior to the onset of neuron loss and an increase in ubiquitinated proteins (J:251814)

• mice exhibit an accumulation of numerous vesicles or vacuoles in neural soma and neurites at 60 weeks of age with many of them double-membraned indicating abnormal accumulation of autophagosomes (J:251814)

♀ • diminished autophagy in atretic follicles, as shown by greatly reduced ovarian LC3-II protein, absence of LC3+ subcellular autophagosomes, and appearance of autofluorescent lipofuscin (J:232676)

impaired macrophage chemotaxis ( J:232676 )

♀ • failed disposal of atretic follicles is associated with impaired migration of ovarian macrophages into atretic follicles

♀ • no invasion of MHC class II IA+ macrophages (which invade early atretic follicles with apoptotic cells) or CD68+ macrophages (which invade atretic follicles after mid-atresia post-wave of apoptosis) is observed, unlike in wild-type controls

♀ • development of autofluorescence in atretic follicles coincides with failed migration of CD68+ macrophages into the same location

abnormal double-strand DNA break repair ( J:251814 )

• mice fail to initiate the repair of rapidly increasing DNA double-strand breaks in stressed cortical and hippocampal neurons after an abrupt aging surge at 40 weeks of age

nervous system

tau protein deposits ( J:251814 )

• 7 of 8 mice show heavy deposition of abnormal tau, that is hyper-phosphorylated, paired helical fragment, and insoluble, in cortical and hippocampal neurons at 65-80 weeks of age

abnormal neuron morphology ( J:251814 )

• vacuoles are often seen in the neuronal soma and neurites of pyramid neurons in the cortex as early as 40 weeks of age

neurodegeneration ( J:251814 )

• neurodegeneration is seen in the cerebral cortex and hippocampus after 60 weeks of age, with heavy loss of neurites/neurons resulting in the disappearance of normal cortical layers and of hippocampal apical dendrite tufts

• however, older mice show no differences in Purkinje cell density in cerebella

hippocampal neuron degeneration ( J:251814 )

• seen after 60 weeks of age

immune system

impaired macrophage chemotaxis ( J:232676 )

♀ • failed disposal of atretic follicles is associated with impaired migration of ovarian macrophages into atretic follicles

♀ • no invasion of MHC class II IA+ macrophages (which invade early atretic follicles with apoptotic cells) or CD68+ macrophages (which invade atretic follicles after mid-atresia post-wave of apoptosis) is observed, unlike in wild-type controls

♀ • development of autofluorescence in atretic follicles coincides with failed migration of CD68+ macrophages into the same location

hematopoietic system

impaired macrophage chemotaxis ( J:232676 )

♀ • failed disposal of atretic follicles is associated with impaired migration of ovarian macrophages into atretic follicles

♀ • no invasion of MHC class II IA+ macrophages (which invade early atretic follicles with apoptotic cells) or CD68+ macrophages (which invade atretic follicles after mid-atresia post-wave of apoptosis) is observed, unlike in wild-type controls

♀ • development of autofluorescence in atretic follicles coincides with failed migration of CD68+ macrophages into the same location

mortality/aging

early reproductive senescence ( J:232676 )

♀ • average reproductive life span (age for last successful delivery of a litter) is shortened to two thirds of that in heterozygous littermates

♀ • females deliver fewer litters than heterozygous littermates (3.15 +/- 0.61 versus 5.90 +/- 0.48) during their entire reproductive life span

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:251814